Chronic fatigue syndrome (CFS) has been a true challenge for the practicing physicians and scientific researchers. The constellation of symptoms is complex and many patients present differently (1, 2). A severe flu-like illness that occurred in the majority of cases of CFS followed by persistent illness and fatigue suggest an infectious etiology triggering and possibly perpetuating this syndrome. In small subsets of patients, Epstein-Barr virus (EBV), Cytomegalovirus (CMV), Parvovirus B19, Brucella, Toxoplasma, Coxiella burnetti and Chlamydia pneumoniae have been reported to cause prolonged fatigue, fevers and many other symptoms of CFS (3-9). However, no direct nexus between these etiological agents and CFS has been established.
Some studies demonstrated circulating antigen of enterovirus and elevated antibody titers (10-15) suggesting a role for enteroviruses in CFS. A number of investigators used DNA/RNA hybridization or polymerase chain reaction (PCR) to detect the presence of enteroviral RNA in the blood and muscles of patients with CFS (17-22). Yousef reported Coxsackie Virus B (CVB) RNA persistence in muscle fibers in 6 out 13 (46%) adult patients with dermatomyositis or polymyositis using in situ hybridization (21). The enteroviral RNA was usually, but not always, found in sections with inflammatory cells. Cunningham tested muscle biopsy specimens from CFS patients to demonstrate that the enteroviral RNA found in patient material had a positive:negative strain ratio of 1:1 rather than the 100:1 ratio found in control enteroviral cultures (22). This result suggested a defect in control of enteroviral RNA synthesis in CFS patients that might permit persistence of the defective virus in these patients. Galbraith et al. extend the above finding by performing phylogenetic analysis of the amplified cDNA from the blood of patients; the sequences closed matched to those found in CVB and Echoviruses (23). A number of other studies have failed to demonstrate amplifiable enteroviral RNA in blood or in other tissue (24-25), although two recent papers again demonstrated the presence of enteroviral RNA in muscle biopsies of CFS patients and not in the controls (26, 27).
The present inventor has recently demonstrated the presence of enteroviral RNA in the peripheral blood leukocytes of 35% of the CFS patients, and the persistence of enteroviral RNA correlated with the severity of illness (28-30). Antiviral treatment with interferon and Ribavirin and the combination of α- and γ-interferon resulted in significant improvement of symptoms and suppression of viral RNA in the blood leukocytes (31-32). The relapse of symptoms and reappearance of viral RNA in the peripheral blood leukocytes after drug discontinuation supported the pathogenic role of enterovirus in CFS.
However, there remains a need for sensitive and specific methods for the diagnosis of chronic enterovirus infection in immunocompetent hosts. Enteroviruses cause acute respiratory and gastrointestinal infections, with subsequent dissemination to the central nervous system, heart and muscles. Previous studies looked for viral products in the blood or in the end-organs have yielded conflicting results. Being acid-resistant, swallowed, infected secretions from upper airway, or virus-contaminated water/food may survive in the stomach and cause acute infections of the stomach. Most of the CFS patients complained of upper and lower gastrointestinal symptoms, which are often referred to as irritable bowel syndrome. Stomach tissue is easily accessible by upper gastrointestinal endoscopy (EGD) and biopsy of the antrum is routinely performed to look for Helicobacter pylori—an established pathogen of the stomach.